Organism | UniProt | Comment | Textmining |
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Homo sapiens | P46934 | - |
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Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
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[Nedd4-1-ubiquitin-conjugating enzyme E2]-S-ubiquitin-L-cysteine + [activated Cdc42-associated tyrosine kinase]-L-lysine | activated Cdc42-associated tyrosine kinase is ubiquitinated by HECT E3 ubiquitin ligase Nedd4-1 and degraded along with epidermal growth factor receptor in response to epidermal growth factor stimulation. Activated Cdc42-associated tyrosine kinase interacts with Nedd4-1 through a conserved PPXY WW-binding motif. The WW3 domain in Nedd4-1 is critical for binding to activated Cdc42-associated tyrosine kinase. Deletion of the sterile alpha motif SAM-domain at the N-terminus dramatically reduces the ubiquitination of activated Cdc42-associated tyrosine kinase by Nedd4-1, while deletion of the Uba domain dramatically enhances the ubiquitination. Activated Cdc42-associated tyrosine kinase degradation is processed by lysosomes, not proteasomes | Homo sapiens | [Nedd4-1ubiquitin-conjugating enzyme E2]-L-cysteine + [activated Cdc42-associated tyrosine kinase]-N6-ubiquitinyl-L-lysine | - |
? | |
[Nedd4-1-ubiquitin-conjugating enzyme E2]-S-ubiquitin-L-cysteine + [epidermal growth factor receptor]-L-lysine | epidermal growth factor receptor and activated Cdc42-associated tyrosine kinase are ubiquitinated by ubiquitin ligase Nedd4-1 in response to epidermal growth factor stimulation | Homo sapiens | [Nedd4-1-ubiquitin-conjugating enzyme E2]-L-cysteine + [epidermal growth factor receptor]-N6-ubiquitinyl-L-lysine | - |
? |
Synonyms | Comment | Organism |
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Nedd4-1 | - |
Homo sapiens |
General Information | Comment | Organism |
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physiological function | RNA interference knockdown of ubiqitin ligase Nedd4-1 inhibits degradation of both epidermal grwoth factor receptor and activated Cdc42-associated tyrosine kinase, and overexpression of activated Cdc42-associated tyrosine kinase mutants that are deficient in either binding to or ubiquitination by Nedd4-1 blocks epidermal growth factor-induced degradation of epidermal growth factor receptor | Homo sapiens |